Splenectomized and sham-operated mice with chronic Schistosoma mansoni infection were compared for the development of periportal fibrosis (pipestem fibrosis). Although this lesion appeared less frequently in splenectomized mice, it also developed in the absence of the spleen. The time of splenectomy, spleen weight, presence of anti-idiotypic antibodies, the number of eggs in the liver, and the type and size of periovular granulomas in the liver as evaluated by computerized morphometry did not show statistically significant differences between the two groups. It is concluded that the role of the spleen in the development of pipestem fibrosis seems ancillary and that multifactorial influences, including worm burden, hepatic vascular adjustment, and factors associated with the biology of extracellular matrix of the liver, probably play a more significant role.